FLT-1 blockade modulates leukemia localization and survival of inoculated recipients. (A) Evidence for distinct BM localization of 697 cells, in untreated recipients or those treated with the neutralizing monoclonal Ab to FLT-1, 6.12 (FLT-1 Ab, administered every 2 days at 500 ng/injection). Bottom panels show evidence for the preferential localization of inoculated 697 cells in the epiphysis of the long bones of NOD-SCID mice (right, × 150 magnification; inset, × 200 magnification), visualized by human TdT staining as described in “Materials and methods.” Note the almost complete absence of TdT staining in the diaphysis of control or KDR Ab-treated mice (bottom left panel, inset). Top panels show BM of long bones of NOD-SCID recipients treated every 2 days with the FLT-1-neutralizing Ab 6.12. Results show a strong accumulation of TdT-positive leukemia cells in the diaphysis of the bone (top left panel, inset), whereas the epiphysis shows no evidence for the presence of 697 cells (top right panel, inset). The results shown are representative of 12 recipients for each condition, as determined in 3 independent experiments. (B) FLT-1 neutralization prolongs the survival of NOD-SCID mice inoculated with ALL cells. The results show a significant increase (P < .05, Kaplan-Meyer curve) in the survival of NOD-SCID mice inoculated with 697 cells and treated every 2 days with the FLT-1-neutralizing Ab 6.12 (FLT-1 Ab, 500 ng/injection). The results shown were obtained from 3 independent experiments (4 mice per condition in all experiments). Image acquisition performed as for Figure 3, except that a PLAN 10 ×/0.25 objective lens was used. Error bars indicate standard deviation.